Importance Active surveillance is noninferior to standard surgery for 2-year survival and improves short-term health-related quality of life among patients with a complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Although active surveillance reduces the upfront costs of surgery and hospital stay, it requires repeated diagnostic tests and, for some patients, delayed surgery and hospitalization during follow-up. Objective To assess the cost-effectiveness of active surveillance compared with standard surgery after nCRT. Design, Setting, and Participants This prespecified cost-effectiveness analysis from a health care perspective conducted at 12 hospitals in the Netherlands as a secondary analysis of the Surgery as Needed for Oesophageal Cancer (SANO) trial, a noninferiority, cluster randomized study, enrolled patients with esophageal cancer who achieved a CCR after nCRT between November 8, 2017, and January 17, 2021, with follow-up for up to 5 years. Data were analyzed on June 1, 2025. Interventions Active surveillance, consisting of repeated response evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months after nCRT, compared with standard surgery. Main Outcome and Measures Incremental cost-effectiveness of active surveillance vs standard surgery and quality-adjusted life-years (QALYs) with 95% CIs up to 5 years were derived with bootstrapping, with 80% of patients (247 of 309) having complete follow-up. Incremental net monetary benefit (iNMB) was calculated at varying willingness-to-pay thresholds. All analyses followed the modified intention-to-treat principle. Costs are given in Euros (currency exchange rate of €1 = US $1.16 as of June 11, 2026). Results Among 309 patients (198 in the active surveillance group; median age, 69 years [IQR, 63-74 years]; 156 men [79%]; and 111 in the standard surgery group; median age, 68 years [IQR, 61-73 years]; 86 men [77%]), those in the active surveillance group had a mean of 2.99 QALYs (95% CI, 2.73-3.26) at 5 years vs 2.88 QALYs (95% CI 2.69-3.06) in the standard surgery group. Mean health care costs per patient at 5 years were €36 733 (95% CI, €33 530-€40 009) in the active surveillance group vs €45 106 (95% CI, €39 449-€51 545) in the standard surgery group. The incremental QALY for active surveillance was 0.11 (95% CI, −0.10 to 0.33) and mean costs were €8374 lower (95% CI, €1792-€15 355) compared with standard surgery. At a willingness-to-pay threshold of €80 000 per QALY, the mean iNMB was €17 568 (95% CI, −€725 to €37 497), indicating that active surveillance is cost-effective. Bootstrap analysis showed that 97% of replications fell in the cost-effective region. Conclusions and Relevance In this secondary analysis of a randomized clinical trial of patients with esophageal cancer achieving a CCR after nCRT, active surveillance was cost-effective over a 5-year horizon compared with standard surgery. Broader implementation of this strategy among appropriately selected patients would most likely reduce health care costs without compromising health outcomes. Trial Registration The Dutch Trial Register: NTR 6803

Background: Statins, widely prescribed for hypercholesterolemia, have demonstrated potential antineoplastic properties in preclinical studies. Despite growing interest in their oncologic effects, the role of statin therapy within curative treatment of esophageal cancer remains unexplored. This study aimed to evaluate the impact of statin use on pathologic complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) in patients undergoing neoadjuvant chemo(radio)therapy followed by esophagectomy. Methods: All consecutive patients with esophageal or gastroesophageal junction cancer who underwent esophagectomy following neoadjuvant therapy between March 1994 and September 2013 were retrospectively analyzed using a prospectively maintained database. Baseline demographic and clinical variables were compared between statin users and non-users. Results: A total of 463 patients were included, of whom 90 (19.4%) were statin users at diagnosis. Neoadjuvant chemotherapy (CT) was administered in 88 patients (19%) and chemoradiotherapy (CRT) in 375 patients (81%). pCR (ypT0N0M0) was achieved in 85 patients (18%), with no statistically significant difference between statin users and non-users (22.2% vs. 17.4%, P=0.29). Median DFS (45 vs. 40 months, P=0.25) and OS (44 vs. 42 months, P=0.28) were also not significantly different between the two groups. However, a non-significant trend toward improved DFS was identified in patients with esophageal adenocarcinoma receiving lipophilic statin therapy. Conclusions: In this cohort, statin use was not associated with improved pathologic response or survival outcomes following neoadjuvant therapy for esophageal cancer. These findings do not support modification or discontinuation of statin therapy in this patient population.

Abstract Topic Esophageal Cancer: Non-Surgical Treatment of Esophageal Cancer Background Active surveillance may be offered as an alternative to standard surgery in patients with clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. While awaiting long-term outcomes of the SANO trial, patients with cCR who opted for active surveillance after decision counseling were registered in the SANO-2 study. Methods The SANO-2 study is a multicenter prospective observational cohort study. Patients with histologically proven resectable esophageal or junctional adenocarcinoma or squamous cell carcinoma treated with CROSS were assessed for clinical response. Patients with a cCR at 12 weeks post-nCRT were offered active surveillance, whereas patients with residual tumour underwent esophagectomy. Patients who gave informed consent and underwent the second clinical response evaluation (CRE-2) between 31 May 2021 and 31 December 2023 were included, allowing for a minimum potential follow-up of 24 months. Follow-up data were censored at 31 December 2025. Overall survival was defined as the interval from the date of cCR (i.e., date of biopsies taken at CRE-2) to all-cause mortality, censored at last follow-up. Survival was estimated using the Kaplan–Meier method. Patient characteristics and outcomes were compared with patients from the SANO trial. Results A total of 415 patients underwent the first clinical response evaluation (CRE-1), of whom 176 patients (42%) achieved cCR at CRE-2. The median age was 69 years (IQR 60-73), 132 patients (75%) were male, and 135 patients (77%) had adenocarcinoma. These and other baseline characteristics of the included patients were largely consistent with those of patients in the SANO trial. The median follow-up time was 30 months (IQR 23–38). During active surveillance, 69 patients (39%) had persistent cCR, 79 patients (45%) developed isolated locoregional regrowth, and 28 patients (16%) developed distant metastases. At 24 months, overall survival was 79% (95% CI 73–85) in patients undergoing active surveillance. Median overall survival was not reached. Conclusion In this multicenter prospective observational cohort study, two-year overall survival on active surveillance was consistent with results from the randomized SANO trial. These findings support an active surveillance strategy in cCR patients after neoadjuvant chemoradiotherapy outside a randomized setting.

OBJECTIVE:To assess pattern of regrowth after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This may inform optimization of response evaluations and explore the possibility for endoscopic treatment of cancer regrowth. SUMMARY BACKGROUND DATA:Active surveillance is a treatment approach for patients with locally advanced esophageal cancer but the timely detection of regrowth remains challenging. METHODS:A retrospective cohort study was conducted in patients with complete clinical response 3 months after nCRT who underwent active surveillance. Patients with cancer regrowth that underwent surgery were included. Resection specimens were reviewed by 2 pathologists. The primary outcome was the anatomic layer(s) of regrowth within the esophageal wall. RESULTS:In total, 75 resection specimens were available 6-36 months after nCRT. Cancer cells were seen in the mucosal layer in 68 of 75 (91%) patients. In 4/75 (5%) patients the tumor was confined to the mucosa. In 13/75 patients (17%), tumor was seen in the mucosa and submucosa but 4 patients also had lymph node involvement. Overall, tumor was present in the submucosa in 88%, proper muscle layer in 71%, and surrounding stroma in 61% of specimens. The majority of regrowth occurred in all layers and this pattern did not change over time. CONCLUSIONS:Detected regrowth after nCRT predominantly involves the mucosa and submucosa in the majority of patients and its temporal regrowth pattern support endoscopy as a diagnostic tool. Given the risk of undetected nodal disease and the current limitations of staging after nCRT, surgery remains the recommended treatment for regrowth.

INTRODUCTION:Socioeconomic status (SES) is associated with disparities in cancer outcomes. The relationship between SES and postoperative outcomes after esophagectomy is inconsistent, especially within low-threshold universal healthcare systems. We hypothesized that lower SES would be associated with higher rates of postoperative complications, and longer length of hospital stay (LOS). MATERIALS AND METHODS:This retrospective nationwide cohort study used Dutch Upper Gastrointestinal Cancer Audit (DUCA) data. All patients aged ≥18 years undergoing esophagectomy between 2014 and 2023 were included. SES was based on neighbourhood-level data derived from Statistics Netherlands (CBS). Patients were assigned to three SES groups (low, middle, high). Outcomes included severe postoperative complications and other postoperative outcomes, including length of stay (LOS) and mortality. Multivariable regression adjusted for confounders. RESULTS:Among 6658 patients, lower SES groups had a higher comorbidity burden, with American Society of Anaesthesiologists (ASA) physical status ≥ III in 32·3% of low SES patients, compared with 27·2% and 26·0% in middle and high SES groups. In univariable analysis, high SES was associated with a lower risk of prolonged intensive care unit (ICU) stay (OR 0·78, 95% CI 0·67-0·91) and LOS (β -1·60 days, 95% CI -2·90 to -0·34). After adjustment, SES was not independently associated with postoperative outcomes. CONCLUSION:SES was not associated with postoperative outcomes after esophagectomy. Lower SES groups had higher comorbidity burden, which may explain the attenuation of the association after adjustment for clinical risk factors. These findings suggest that within a low-threshold universal healthcare system, postoperative outcomes after esophagectomy may be primarily determined by clinical factors rather than SES.

Gastroesophageal cancer has a poor prognosis, and treatment significantly impacts health-related quality of life (HRQoL). Accurate prediction of HRQoL changes after treatment can support shared decision-making. This study aimed to develop and validate HRQoL prediction models for patients with gastroesophageal cancer using established risk-prediction models and a newly proposed sequential score model. HRQoL data came from the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients registry, linked to the Netherlands Cancer Registry. The EORTC QLQ-C30 functioning scales were used as outcomes. Risk-prediction models, based on logistic elastic-net regression, estimated the probability of meaningful HRQoL deterioration at 3, 6, and 12 months post-treatment. The sequential score model, using XGBoost regression, predicted the next HRQoL score at any time. Calibration curves and integrated calibration index (ICI) assessed predictive performance, with Brier scores and AUC for risk-prediction models and root mean squared error plus Out-of-Sample r² for sequential models. Risk-prediction models showed strong performance (ICI: 0.03–0.08; Brier score: 0.09–0.17; AUC: 0.79–0.87) for predicting significant deterioration in Summary Score, Physical Functioning, and Fatigue, with good calibration. Sequential score models explained up to 40

BACKGROUND:The Surgery As Needed for Oesophageal cancer(SANO) trial showed that one third of patients with resectable, locally advanced esophageal carcinoma achieved complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) and were eligible for active surveillance. However, determining CCR remains challenging, and the optimal approach for patients with uncertain tumor response at restaging after nCRT has not been established. This study investigated the pathological outcomes of these patients. METHODS:Patients from the SANO cohort with non-traversable lesions, high-grade dysplasia (HGD) or clinical suspicion of residual tumor without (cyto-)histological confirmation at clinical response evaluations 4-12 weeks after nCRT were included. The primary endpoint was the complete pathological response rate after resection. RESULTS:A total of 272 patients had an uncertain tumor response at restaging: 94 with non-traversable lesions, 50 with HGD, and 128 with clinical suspicion of residual tumor. Of these, 205 underwent esophagectomy, and 15% (95%CI 10-20) had a complete pathological response. The complete pathological response rates were 26% (19/73, 95%CI 17-37) for the non-traversable lesions group, 10% (4/42, 95%CI 4-22) for the HGD group, and 8% (7/90, 95%CI 4-15) for the clinical suspicion group. The highest rate of complete pathological response was observed in patients with squamous cell carcinoma and non-traversable lesions (33%, 14/42, 95%CI 21-48). CONCLUSION:Esophagectomy should be advised for most patients with an uncertain tumor response after nCRT, as 85% have residual disease. One-third of patients with squamous cell carcinoma and non-traversable lesions on endoscopic assessment achieved a complete pathological response, which should be considered in shared decision-making following restaging.

There is substantial global variation in demographics, disease burden, and treatment for gastric cancer patients. Benchmarking is an instrument to assess such variation and enables to investigate to which extent case-mix and treatments explain differences in outcomes. We aimed to evaluate hospital-level variation in surgical outcomes following gastrectomy for gastric cancer before and after adjusting for case-mix and treatment-related factors. Data were retrieved from the GastroBenchmark and GASTRODATA databases, including consecutive gastric cancer resections performed between 2017 and 2021 from 43 centers. Patients who underwent a (sub)total gastrectomy for adenocarcinoma were identified. Outcomes included 30-day mortality, severe complications (Clavien-Dindo grade ≥ 3a), > 15 lymph nodes retrieved, negative resection margin (R0), prolonged hospitalization (> 14 days), readmissions (< 30 days), reoperations, and escalation of care. We assessed absolute inter-hospital variation for outcomes, and estimated outcomes using mixed-effect logistic regression models with a random intercept. We estimated crude, case-mix adjusted, and case-mix and treatment adjusted hospital effects. The conditional and marginal pseudo-R2 were used to quantify the variance in outcome explained by case-mix and treatment-related factors. A total of 7818 patients from 41 hospitals were included, with contributions ranging from 12 to 2554 patients per hospital (IQR: 49–146). Observed 30-day mortality and severe complications ranged from 0 to 9.7

Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal/junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. This study aimed to evaluate the feasibility and safety of TNT FLOT-CROSS. Patients with histologically proven esophageal/junctional adenocarcinoma with oligometastases (maximum four lesions in maximum two organs) were included. Treatment consisted of four cycles of FLOT followed by response evaluation (CT-scan). Patients without disease progression proceeded to CROSS, followed by response evaluation (CT-scan, endoscopy with biopsies and endoscopic ultrasonography with fine-needle aspiration on indication). Primary endpoint was the safety and tolerability of TNT FLOT-CROSS. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), quality of life (QoL) using QLQ-C30 and QLQ-OG25, toxicity and the proportion of patients proceeding to local therapy. Twenty patients were included of whom 16 (80%) had a single metastatic lesion. Median follow-up was 47.9 months (95% CI 32.8-63.1). Fifteen patients (75%) completed TNT FLOT-CROSS. FLOT came with manageable, expected toxicity, and all patients without progression were able to start and complete CROSS. No grade 3-5 toxicities occurred during CROSS. After TNT FLOT-CROSS, two patients underwent surgery. The 1- and 2-year PFS were 40% and 13%, respectively. Three months after TNT FLOT-CROSS completion, DCR was 55%. Dysphagia scores significantly decreased over time, while fatigue significantly increased. Sequencing TNT FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity and promising efficacy, with a 1-year progression free survival of 40%. Trial Registration: Dutch trial register, NL9269.

Background:In the Netherlands, all inhabitants are required to have health insurance that covers standard medical care. While this regulated system aims to ensure equal access, recent evidence suggests that socioeconomic status (SES) disparities still exist. This study investigates SES-related differences in treatment and survival among patients with gastric or oesophageal cancer. Methods:This nationwide population-based study included gastroesophageal cancer patients diagnosed in 2015-2022. Patients were stratified into three SES-groups using median disposable household income per postal code area, an additional stratification was performed by histological subtype. Multivariable logistic regression was used to assess the likelihood of receiving specific treatments for different tumour types. Age-standardized relative survival was calculated as the ratio of observed survival to expected survival based on age, sex, calendar year, and median household income group in the general population. Findings:In total, 30,184 gastroesophageal cancer patients were categorized. In curable gastric cancer, patients with middle income had a significantly higher likelihood of receiving surgery compared to low income (OR 1.48 (95% CI 1.21-1.80), p < 0.001). For oesophageal cancer, both middle- (OR 1.17 (95% CI 1.05-1.30), p < 0.001) and high-income patients (OR 1.27 (95% CI 1.13-1.43), p < 0.001) were more likely to undergo surgery than those with low income. In palliative settings, middle- and high-income patients were also more likely to receive systemic therapy, in oesophageal cancer (OR 1.38 (95% CI 1.21-1.57), p < 0.001; OR 1.53 (95% CI 1.34-1.74), p < 0.001) and in gastric for high income (OR 1.27 (95% CI 1.05-1.55), p = 0.014). Relative survival analyses further demonstrated that middle- and high-income groups consistently had higher median, and 5-year survival compared to the low-income group. Interpretation:Despite universal health insurance, socioeconomic disparities in treatment and survival of gastroesophageal cancer patients persist in the Netherlands, reflecting not inequitable access but broader life-course health disparities that influence treatment fitness and outcomes. These findings highlight the need to address broader social and systemic determinants to improve equity in cancer care, in the Netherlands and globally. Funding:This study received no funding.

Objective: To assess pattern of regrowth after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This may inform optimization of response evaluations and explore the possibility for endoscopic treatment of cancer regrowth. Summary Background Data: Active surveillance is a treatment approach for patients with locally advanced esophageal cancer but the timely detection of regrowth remains challenging. Methods: A retrospective cohort study was conducted in patients with complete clinical response 3 months after nCRT who underwent active surveillance. Patients with cancer regrowth that underwent surgery were included. Resection specimens were reviewed by 2 pathologists. The primary outcome was the anatomic layer(s) of regrowth within the esophageal wall. Results: In total, 75 resection specimens were available 6–36 months after nCRT. Cancer cells were seen in the mucosal layer in 68 of 75 (91%) patients. In 4/75 (5%) patients the tumor was confined to the mucosa. In 13/75 patients (17%), tumor was seen in the mucosa and submucosa but 4 patients also had lymph node involvement. Overall, tumor was present in the submucosa in 88%, proper muscle layer in 71%, and surrounding stroma in 61% of specimens. The majority of regrowth occurred in all layers and this pattern did not change over time. Conclusions: Detected regrowth after nCRT predominantly involves the mucosa and submucosa in the majority of patients and its temporal regrowth pattern support endoscopy as a diagnostic tool. Given the risk of undetected nodal disease and the current limitations of staging after nCRT, surgery remains the recommended treatment for regrowth.

Identifying patients with similar health-related quality of life (HRQoL) recovery patterns can guide more effective disease management. This study aimed to identify cross-sectional and longitudinal HRQoL profiles in esophageal cancer patients, and to examine associations with demographic and clinical characteristics. Longitudinal data from the Prospective Observational Cohort Study of Esophageal-gastric cancer Patients (POCOP) were analyzed. Patients treated with chemoradiation (CRT), with/without surgery, were followed for 12 months post-treatment. HRQoL was measured pre-treatment, at 6- and 12-months using validated questionnaires (i.e., EORTC QLQ-C30, QLQ-OG25, and HADS). Latent Profile and Latent Transition analyses were used to identify cross-sectional and longitudinal profiles, respectively. Regression analyses explored their associations with demographic and clinical characteristics. Of the 605 patients (mean age: 66.6 (SD: 8.0) years), most were male (82

Importance:Active surveillance is noninferior to standard surgery for 2-year survival and improves short-term health-related quality of life among patients with a complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Although active surveillance reduces the upfront costs of surgery and hospital stay, it requires repeated diagnostic tests and, for some patients, delayed surgery and hospitalization during follow-up. Objective:To assess the cost-effectiveness of active surveillance compared with standard surgery after nCRT. Design, Setting, and Participants:This prespecified cost-effectiveness analysis from a health care perspective conducted at 12 hospitals in the Netherlands as a secondary analysis of the Surgery as Needed for Oesophageal Cancer (SANO) trial, a noninferiority, cluster randomized study, enrolled patients with esophageal cancer who achieved a CCR after nCRT between November 8, 2017, and January 17, 2021, with follow-up for up to 5 years. Data were analyzed on June 1, 2025. Interventions:Active surveillance, consisting of repeated response evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months after nCRT, compared with standard surgery. Main Outcome and Measures:Incremental cost-effectiveness of active surveillance vs standard surgery and quality-adjusted life-years (QALYs) with 95% CIs up to 5 years were derived with bootstrapping, with 80% of patients (247 of 309) having complete follow-up. Incremental net monetary benefit (iNMB) was calculated at varying willingness-to-pay thresholds. All analyses followed the modified intention-to-treat principle. Costs are given in Euros (currency exchange rate of €1 = US $1.16 as of June 11, 2026). Results:Among 309 patients (198 in the active surveillance group; median age, 69 years [IQR, 63-74 years]; 156 men [79%]; and 111 in the standard surgery group; median age, 68 years [IQR, 61-73 years]; 86 men [77%]), those in the active surveillance group had a mean of 2.99 QALYs (95% CI, 2.73-3.26) at 5 years vs 2.88 QALYs (95% CI 2.69-3.06) in the standard surgery group. Mean health care costs per patient at 5 years were €36 733 (95% CI, €33 530-€40 009) in the active surveillance group vs €45 106 (95% CI, €39 449-€51 545) in the standard surgery group. The incremental QALY for active surveillance was 0.11 (95% CI, -0.10 to 0.33) and mean costs were €8374 lower (95% CI, €1792-€15 355) compared with standard surgery. At a willingness-to-pay threshold of €80 000 per QALY, the mean iNMB was €17 568 (95% CI, -€725 to €37 497), indicating that active surveillance is cost-effective. Bootstrap analysis showed that 97% of replications fell in the cost-effective region. Conclusions and Relevance:In this secondary analysis of a randomized clinical trial of patients with esophageal cancer achieving a CCR after nCRT, active surveillance was cost-effective over a 5-year horizon compared with standard surgery. Broader implementation of this strategy among appropriately selected patients would most likely reduce health care costs without compromising health outcomes. Trial Registration:The Dutch Trial Register: NTR 6803.

While postoperative complications are established predictors of readmission after esophagectomy, reasons for readmission are still elusive, specifically in patients without complications during the index admission. This study assessed reasons for readmission and explored potential predictors in this lower-risk subgroup. A retrospective multicenter cohort study included all patients ≥18 years who underwent curative esophagectomy between 2020 and 2023 across three Dutch hospitals. Patients with in-hospital mortality or missing readmission data were excluded. The primary outcome was the reason for 30-day readmission. Secondary outcome was the identification of risk factors for readmission using uni- and multivariable logistic regression. Of 663 patients, 350 (52.8%) had an uncomplicated index admission, with a 30-day readmission rate of 12.6% (44/350). The most common causes for readmission were anastomotic leakage (32.6%), pulmonary complications (20.9%), insufficient intake (14.0%), and infections (14.0%). No significant associations were found with age, sex, the American Society of Anesthesiologists (ASA) classification, Charlson Comorbidity Index, tube feeding, length of stay, or surgical approach. Among patients readmitted with anastomotic leakage, 11/14 had met functional recovery criteria at discharge. Three patients had unexplained subtle increases in C-reactive protein (CRP) or leukocyte count. Three patients underwent a computed tomography (CT) scan during the index admission. Readmission remains common, even in patients with an initially uneventful recovery, and is frequently caused by undetected or delayed complications including anastomotic leakage. Traditional predictors did not identify patients at risk for readmission in this cohort. Subtle deviations before discharge may represent early warning signs and require validation in future prospective research.

Cervical lymph node metastasis in thoracic esophageal cancer occupies a conceptual border zone between locoregional and distant disease. Evidence guiding treatment selection in this population remains limited in Western cohorts. The objective was to evaluate treatment strategies and overall survival outcomes for patients with resectable esophageal cancer and concurrent cervical lymph node metastasis in the Netherlands. This population-based cohort study used the Netherlands Cancer Registry to identify patients with resectable thoracic esophageal or gastroesophageal junction cancer and concurrent cervical lymph node metastasis. Treatment strategies included definitive chemoradiotherapy, neoadjuvant therapy followed by surgery, chemotherapy with or without limited radiotherapy (≤30 Gy), palliative radiotherapy, and best supportive care. Kaplan-Meier analysis and Cox regression adjusted with inverse probability of treatment weighting (IPTW) were used to assess overall survival and treatment effects. Between 2015 and 2021, 412 eligible patients were identified. Median overall survival was 24 months for patients treated with neoadjuvant therapy followed by surgery, 18 months for definitive chemoradiotherapy, 15 months for chemotherapy, 7 months for radiotherapy alone, and 3 months for best supportive care. In multivariable analysis, neoadjuvant therapy followed by surgery was associated with longer survival compared with definitive chemoradiotherapy (HR 0.56 [0.34-0.91]). Similar estimates were observed after IPTW. Higher cN stage and poorer performance status were independently associated with worse survival. Subgroup analysis of neoadjuvant chemoradiotherapy versus chemotherapy within the surgical cohort showed no significant survival difference. In this nationwide cohort, management of thoracic esophageal cancer with concurrent cervical lymph node metastasis was highly heterogeneous. Although neoadjuvant therapy followed by surgery was associated with longer survival, interpretation is limited by baseline differences and potential residual confounding. These findings suggest that surgery may be considered within a multimodality strategy in carefully selected patients and warrant prospective evaluation to better define its role.

Background The peritoneum is a common metastatic site in gastric cancer. The prognosis of synchronous peritoneal metastases compared to other metastatic sites in gastric cancer remains understudied. This study aims to evaluate the impact of peritoneal metastases on survival in patients with metastatic gastric cancer. Methods Patients with gastric cancer and synchronous metastases between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Patients were categorized based on the site of metastases. Median overall survival (OS) was calculated for each metastatic site group. Multivariable Cox regression analyses were performed to evaluate the association between patient, tumour, and treatment characteristics, including the impact of systemic therapy, on OS. Findings A total of 4072 patients were included, of whom 1835 (45.1%) had peritoneal metastases. Of these, 58.1% had isolated peritoneal metastases. For patients with metastatic gastric cancer treated with systemic therapy, the median OS was 9.0 months (95% confidence interval (CI): 8.6-9.5), compared to 1.7 months (95% CI: 1.7-1.9) for treatment-na & iuml;ve patients, who received only palliative care. The survival for patients with isolated peritoneal metastases (4.4 months, 95% CI: 4.0-4.8 months) was similar to those with isolated non-peritoneal metastases (4.6 months, 95% CI: 4.2-5.1 months, adjusted HR: 0.94, 95% CI: 0.86-1.03, p = 0.185). Systemic therapy was associated with comparable survival in patients with peritoneal metastases and those with metastases at other sites. Interpretation This study demonstrates that there is no statistically significant difference in survival between patients with isolated peritoneal metastases and those with isolated non-peritoneal metastases in gastric cancer. Our findings emphasize the unique prognostic landscape for peritoneal metastases in gastric cancer, underscoring the need for disease-specific evaluations, rather than relying on assumptions derived from other cancer types.

Background: Neoadjuvant chemoradiotherapy (nCRT) or perioperative chemotherapy followed by surgical resection is the standard of care for oesophageal and gastroesophageal junction cancer. Up to a third of patients will have a pathological complete response to neoadjuvant treatment. Given the significant morbidity associated with surgery, active surveillance is considered as a potential alternative for patients with clinical complete response post-nCRT. Summary: The preSANO and preSINO trials have validated a multimodal diagnostic strategy combining oesophagogastroduodenoscopy with bite-on-bite biopsies, endoscopic ultrasonography with fine-needle aspiration of suspicious lymph nodes, and PET-CT to detect residual disease. The SANO trial is assessing whether active surveillance leads to non-inferior overall survival compared to planned surgery. Early results of randomized studies support previous retrospective reports of comparable oncological outcomes, with improved quality of life in the surveillance group. Despite concerns of increased morbidity of postponed surgery upon recurrence, recent data indicate comparable surgical outcomes of delayed oesophagectomy. Ongoing trials, including SANO-2, CELEAC, and NEEDS, aim to rationalize surveillance protocols, while SANO-3 is investigating the role of adding immunotherapy in improving response durability. Key Messages: Active surveillance represents a promising alternative to surgery for oesophageal cancer patients achieving complete clinical response after neoadjuvant therapy. While it can spare patients the morbidity of oesophagectomy and significantly improve quality of life, it requires accurate response assessment and structured follow-up. Future developments, including immunotherapy and non-invasive diagnostics, may further refine this approach and expand its safe applicability. .

INTRODUCTION:This study aimed to evaluate whether the retrieval of 15 or more lymph nodes (LN) during gastrectomy for cancer is associated with better survival and more accurate pathological staging. METHODS:Patients that underwent gastrectomy between 2011 and 2016 were reviewed from the Dutch Upper Gastrointestinal Cancer Audit. Patients with <15 and ≥15 LN retrieved were compared after propensity-score matching based on patient and tumor characteristics. The primary endpoint was 3-year overall survival. RESULTS:A total of 2,047 patients were included in the study. After propensity score matching, 522 patients with ≥15 LNs were matched to 522 patients with <15 LNs. There was no statistically significant difference in overall survival between both groups with 3-year survival rates of 56% versus 59%, respectively. Patients with ≥15 LNs had a more advanced pN-category. While median survival was higher for patients with ≥15 LNs versus <15 LNs in the subgroups pN2, pN3a, and pN3b, no statistically significant differences were found. Similar results were found in the propensity score matched cohort using 23 LNs as cut-off. CONCLUSION:≥15 LNs retrieved during gastrectomy for cancer was associated with higher pN-stage, likely as a result of stage migration. Three-year overall survival was comparable for patients with ≥15 LNs and patients with <15 LNs retrieved.